Synthesis and SAR Evaluation of Mercaptotriazolo derivatives as anti-inflammatory agents.

Abstract

A new series of benzothiazole appended triazole derivatives were synthesized. Characterization is done by FT-IR, Mass, 1H and 13C NMR spectroscopic techniques. The newly synthesized compounds were screened for antioxidant and anti inflammatory activities. Experimental data hypothesized compound 7b as highly potent cytotoxicant with lengthened activity. Structure–activity relation interrelates the biological activity and chemical moiety of the molecule. Structurally, 7b is a benzothiazolyltriazole having a pyrrolidine group (five membered ring) attached to two CH2 groups and methyl substituent at 7th position of the benzothiazole ring

[1,2,4]Triazolo[3,4-b]benzothiazole scaffold as versatile nicotinamide mimic allowing nanomolar inhibition of different PARP enzymes

“…44,50 In this paper, we initially discovered compound 1, based on a new nicotinamide mimic scaffold, TBT, which was able to inhibit multiple PARP enzymes at micromolar potency. The TBT is an underexplored scaffold in medicinal chemistry, with few examples of compounds with antifungal, 51 anticonvulsant 52 or anti-inflammatory 53 properties. Most importantly, no PARPi based on this scaffold have been reported until now.…”

“…All starting materials, reagents, and solvents were purchased from common commercial suppliers and were used as such without further purification. Compounds 2 59 , 7 60 , 11 52 , 16 52 , 19 61 , 20 53 , 33 62 , 44 63 , 45 64 , 46 65 , 48 63 , 49 66 , 50 67 , 51 68 , 52 69 , 53 68 , 54 70 , 55 71 , 56 71 , 58 70 , 59 70 , 60 72 , 61 73 , 62 69 , 63 70 , 64 74 , 68 74 , 69 74 , 70 74 , 73 74 , 77-79 75 , 80 76 , 81 77 , and 82 69 were prepared as described in literature. Organic solutions were dried over anhydrous Na 2 SO 4 and concentrated with rotary evaporator at low pressure.…”

“…K 2 CO 3 (0.21 g, 1.5 mmol) and MeI (0.1 mL, 1 mmol) were added under nitrogen atmosphere to a solution of 20 53 (0.11 g, 0.5 mmol) in dry DMF (6 mL). The reaction mixture was stirred at 80 °C for 1.5 h and then poured in ice/water.…”

“…A suspension of 20 53 (0.12 g, 0.54 mmol) and KOH (0.03 g, 0.54 mmol) in absolute EtOH (8 mL) was refluxed for 30 minutes under nitrogen atmosphere. Then, p -chlorobenzyl chloride (0.09 g, 0.54 mmol) was added and the reaction mixture was stirred at reflux.…”

Oxidative Cyclization of 4‐(2‐Mercaptophenyl)‐Substituted 4H‐1,2,4‐Triazolium Species to Tricyclic Benzothiazolium Salts

“…Among these molecules are several fused nitrogen‐ and sulfur‐containing heterocyclic anti‐cancer agents incorporating a (benzo)thiazole fragment, [10–22] a thiadiazole ring, [23–28] or a thiadiazine unit [27–29] . The same scaffolds can be found in molecules with antibacterial, antimicrobial and antifungal properties, [22,30–35] prospective therapeutic agents used to treat asthma or chronic obstructive pulmonary disease, [36–38] molecules with anti‐inflammatory activity, [39] compounds with antidiabetic activity, [40,41] and promising therapeutics to treat Alzheimer's disease [42–44] or schizophrenia [45] …”